Technical Report Documentation Page
Carisoprodol (and Meprobamate)
Gamma-Hydroxybutyrate (GHB, GBL,
Lysergic acid diethylamide (LSD)
Methamphetamine (and Amphetamine)
Morphine (and Heroin)
Zolpidem (and Zaleplon, Zopiclone)
Biographical Sketches of Lead
Authors and Main Contributors
MDMA is a white, tan or brown powder. Available primarily in tablet
ecstasy, ADAM, candy canes, disco biscuit, doves, E, eckie, essence,
hug drug, love drug, M&M, rolls, white doves, X, XTC.
Source: MDMA is the methylenedioxy derivative
of methamphetamine. Starting materials in its illicit manufacture include
isosafrole (Leuckart reaction) and safrole (Merck patent). MDMA is most
commonly found in tablet forms of various colors, carrying distinctive
markings on one side such as a dove, E, yin/yang symbol, Mitsubishi
symbol, etc. MDMA is a Schedule I controlled substance.
Drug Class: Mild CNS stimulant, empathogen,
entactogen, mild hallucinogen and psychedelic, appetite suppressant.
Medical and Recreational Uses: Originally
patented as an appetite suppressant and used as a possible adjunct to
psychotherapy, there is currently no legitimate medical use in the U.
S. MDMA is recreationally used as a party, rave or dance drug for its
stimulant, mild hallucinogenic, and empathogenic properties.
Potency, Purity and Dose: MDMA exists as
a racemic mixture, with the S-(+)-enantiomer having greater CNS potency
compared to the R-(-)-enantiomer. Potency of street samples is highly
variable, and tablets sold as ‘ecstasy’ may in fact contain
little or no MDMA, but may contain caffeine, ephedrine, phenylpropanolamine,
paramethoxyamphetamine (PMA), methylenedioxyamphetamine (MDA), dextromethorphan,
amphetamine, methamphetamine, and ketamine. Some tablets have been reported
to contain LSD or heroin. Typical doses in a series of pills can range
between 10–150 mg of MDMA. User surveys report a range of doses
between 50-700 mg in a session, with an average of 120 mg. Most common
pattern of use is binge consumption at all night rave or dance parties.
MDMA is frequently taken with other recreational drugs such as ethanol,
marijuana, cocaine, methamphetamine, nitrous oxide, and GHB.
Route of Administration: Primarily oral
administration, although MDMA could conceivably be dissolved and injected,
or crushed and snorted.
Pharmacodynamics: MDMA is a phenylethylamine
that has stimulant as well as psychedelic effects. MDMA is related in
structure and effects to methamphetamine, however, it has significantly
less CNS stimulant properties than methamphetamine. MDMA has a high
affinity for 5-HT 2 receptors. Both S- and R- enantiomers of MDMA cause
acute depletion of presynaptic serotonin (5-HT), depression of 5-HT
synthesis by tryptophan hydroxylase, and retrograde destruction of 5-HT
neurons following high doses. MDMA also increases levels of norepinephrine
and dopamine. The MDMA metabolite, S-(+)- MDA, elicits more stereotypic
behavior and is an even more potent neurotoxin than the parent drug.
MDA destroys serotonin-producing neurons which play a direct role in
regulating aggression, mood, sexual activity, sleep, and sensitivity
Pharmacokinetics: MDMA is rapidly absorbed
and t he half-life of MDMA is ~ 7 hours, although non-linear pharmacokinetics
have been observed due to stereoselective pharmacokinetics of the enantiomers.
MDMA is metabolized to MDA which is the only metabolite reported in
blood and plasma. S-(+)- MDA accumulates in blood due to stereoselective
metabolism of S-(+)-MDMA. MDA is further metabolized to its 3-hydroxy-4-methoxy
and 3,4-dihydroxy derivatives (HMA and HHA). Additional MDMA metabolites
include 3-hydroxy-4-methoxymethamphetamine (HMMA) and 3,4-dihydroxymethamphetamine
(HHMA). These polar hydroxylated metabolites are conjugated prior to
their excretion in urine.
Molecular Interaction / Receptor Chemistry: The
majority of MDMA N-demethylation to MDA is via the cytochrome P450 2D6
isoenzyme, with minor contributions by the 1A2 isoform. Potential inhibitors
of these isoenzymes could decrease the rate of MDMA elimination if administered concurrently,
while potential inducers could increase the rate of elimination. Both
extensive and poor MDMA metabolizers have been identified.
Blood to Plasma Concentration Ratio: Data
Interpretation of Blood Concentrations: No
clear correlation exists between MDMA blood concentrations and effects.
MDMA and MDA are the analytes detected in blood, with MDA concentrations
typically only 5-10% of the corresponding MDMA concentrations. Higher
MDA:MDMA ratios may indicate co-administration of MDA. Plasma concentrations
following single oral doses of 50, 75, 100, 125 and 150 mg of MDMA were
0.02-0.08 mg/L, 0.13 mg/L, 0.19-0.21 mg/L, 0.24 mg/L, and 0.44 mg/L,
respectively. Peak concentrations of MDMA and MDA are observed at 1.5-2
hours and 4 hours, respectively.
Interpretation of Urine Test Results: MDMA,
MDA, HMMA, HHMA, HMA and HHA are typically found in urine following
their hydrolysis. MDA and HMMA concentrations in urine are typically
10-15% of the corresponding MDMA concentrations.
Psychological: Low to moderate doses (50-200 mg) produce
mild intoxication, relaxation, euphoria, an excited calm or peace, feelings
of well-being, increase in physical and emotional energy, increased
sociability and closeness, heightened sensitivity, increased responsiveness
to touch, changes in perception, and empathy. At higher doses, agitation,
panic attacks, and illusory or hallucinatory experiences may occur.
Physiological: Low to moderate doses (50-200 mg) produce
mild visual disturbances (blurred or double vision, increased light
sensitivity), dilated pupils, dry mouth, sweating, ataxia, muscle tension,
and involuntary jaw clenching.
Side Effect Profile: Impairment of cognitive,
perception, and mental associations. Psychological difficulties include
confusion, depression, sleep problems, drug craving, severe anxiety,
and paranoia. Subjects may experience fatigue, uncoordinated gait, decreased
fine motor skills, attentional dysfunction (difficulty to maintain attention
during complex tasks),
preoccupation, hyperthermia, tachycardia, hyperthermia,
hyponatremia, convulsions, and catatonic stupor. Prolonged cognitive
and behavioral effects may occur including poor memory recall, flashbacks,
panic attacks, psychosis, and depersonalization due to serotonergic
neuron damage and decreased serotonin production as a result of long-term
Duration of Effects: Following oral administration,
effects onset in 20-30 minutes and desired effects may last only an
hour or more, depending on dose. Other general effects last for approximately
2-3 hours. LSD is sometimes used in combination with MDMA to increase
its duration of effects. Residual and unwanted effects are generally
gone within 24 hours although confusion, depression and anxiety may
last several weeks.
Tolerance, Dependence and Withdrawal Effect: Drug
stacking refers to the ingestion of single doses consecutively as effects
begin to wane, similar to cocaine or methamphetamine binges. Such extensive
or binge use usually occurs over weekends, and can result in exhaustion,
apathy, depression, irritability, insomnia and muscle tension early
the next week (often referred to as “terrible Tuesdays”).
Tolerance does develop, however, the occurrence of physical and/or psychological
dependence is unknown. Persistent neurological deficits may occur, including
serotonergic neuron damage which leads to less production of serotonin.
Drug Interactions: The dopamine D 2 receptor
antagonist, haloperidol, attenuates psychological effects of MDMA but
has no effect on physiological effects.
Performance Effects: MDMA can enhance impulsivity
and make it difficult for a person to maintain attention during complex
tasks (selective attention, divided and sustained attention, and complex
attention tasks). Laboratory studies have demonstrated changes in cognitive,
perception and mental associations, instability, uncoordinated gait,
and poor memory recall. Distortion of perception, thinking, and memory,
impaired tracking ability, disorientation to time and place, and slow
reactions are also known performance effects. Single oral doses of MDMA
causes subjective excitability, anxiety, perceptual changes, and thought
disorders 1-3 hours post dose.
Effects on Driving: In an advanced driving
simulator study, subjects were given a mean single dose of 56 mg MDMA.
Compared to a sober state, moderate effects on vehicle control, acceptance
of higher levels of risk, acute changes in cognitive performance, and
impaired information processing ability were observed. In six subjects
arrested for driving under the influence, MDMA was the only drug detected
at blood concentrations ranging from <0.05-0.58 mg/L. The subjects
were cooperative and laid back, and experienced muscle twitching, body
tremors, perspiring, dilated pupils, slow reaction to light, and poor
performance on field sobriety tests. The following concentrations of
MDMA have also been measured in other retrospective studies; serum MDMA
concentrations ranging from 0.001-0.514 mg/L (mean 0.076 mg/L) in 18
cases of driving impairment; blood MDMA concentrations ranging from
0.04-0.38 mg/L (mean 0.18±0.14 mg/L; median 0.19 mg/L) in 9 impaired
driving cases; blood MDMA concentrations of 0.12, 0.08, and 0.14 mg/L
in 3 impaired driving cases; and a blood MDMA concentration of 2.14
mg/L and urine 118.8 mg/L in one driving fatality case. Another study
reported the occurrence of speeding, jumping red lights, hallucinations/delusions,
and a sense of detachment in five impaired driving cases, however, no
MDMA concentrations were mentioned.
DEC Category: Hallucinogen; (with many characteristics
similar to a CNS stimulant)
DEC Profile: Horizontal gaze nystagmus
not present; vertical gaze nystagmus not present; lack of convergence
not present; pupil size dilated; reaction to light slow; pulse rate
elevated; blood pressure normal to elevated; body temperature normal
to elevated. Other characteristic indicators may include profuse sweating,
muscle twitching, body tremors, and poor performance in field sobriety
tests. Subjects are usually described as very cooperative and “laid-back”.
Note that elevated blood pressure and body temperature are not always
Panel’s Assessment of Driving Risks: Low
to moderate single doses of MDMA can cause acute changes in cognitive
performance and impair information processing, which in turn would impair
driving ability. Basic vehicle control is only moderately affected,
however, subjects may accept higher levels of risk.
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